System for forming emulsions

• US 9,089,844 B2
• Filed: 11/01/2011
• Issued: 07/28/2015
• Est. Priority Date: 11/01/2010
• Status: Active Grant

• Current Assignee: Bio-Rad Laboratories Incorporated
• Original Assignee: Bio-Rad Laboratories Incorporated
• Inventors: Hiddessen, Amy L., Masquelier, Donald A., Ness, Kevin D., Hindson, Benjamin J., Makarewicz, Anthony J. Jr., Chia, Erin R.
• Primary Examiner(s): Merkling, Sally
• Application Number:
  US13/287,120
• Publication Number:
  US 20120152369A1
• Time in Patent Office: 1,365 Days
• US Class Current: 1/1
• CPC Class Codes: B01F 23/41 Emulsifying
• CPC Class Codes: B01F 33/3011 using a sheathing stream of a fluid surrounding a central stream of a different fluid, e.g. for reducing the cross-section of the central stream or to produce droplets from the central stream
• CPC Class Codes: B01F 33/813 mixing simultaneously in two or more mixing receptacles
• CPC Class Codes: B01L 2200/0605 Metering of fluids
• CPC Class Codes: B01L 2200/0673 Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 3/502761 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: B01L 3/502784 specially adapted for droplet or plug flow, e.g. digital microfluidics automatic analysis using a stream of discrete samples in a tube system G01N35/08
• CPC Class Codes: G01N 1/38 Diluting, dispersing or mixing samples
• CPC Class Codes: G01N 2035/1046 Levitated, suspended drops
• CPC Class Codes: Y10T 137/0396 Involving pressure control
• CPC Class Codes: Y10T 137/8593 Systems

Abstract

System, including methods, apparatus, and kits, for forming emulsions. The system may include an instrument and a microfluidic chip received by the instrument. The instrument may apply pressure to prospective emulsion phases held by the chip, to drive formation and collection of emulsions in the chip. In some embodiments, the instrument may stop applying pressure to the chip when a change in pressure meeting a predefined condition is detected by the instrument. The change may indicate that an endpoint of droplet generation has been reached.

Claims

1. A system for emulsion formation, comprising:

a microfluidic device having a plurality of emulsion formation units each including a sample well, a droplet well, a sample inlet channel extending from the sample well to a channel intersection, and a droplet outlet channel extending from the channel intersection to the droplet well; and

an instrument that operatively receives the microfluidic device and including a fluidics assembly having a pressure sensor, the instrument being configured (a) to apply pressure to the emulsion formation units in parallel with the fluidics assembly to drive parallel generation of droplets at the channel intersections of the emulsion formation units and parallel collection of emulsions of the droplets in the droplet wells of the emulsion formation units, (b) to monitor the pressure with the pressure sensor, and (c) to stop application of the pressure to all of the emulsion formation units when the pressure sensor detects a change in pressure indicative of air entering any one of the sample inlet channels from a corresponding sample well.

2. The system of claim 1, further comprising a gasket defining a plurality of orifices configured to provide fluid communication between the microfluidic device and the fluidics assembly such that pressure can be applied to the emulsion formation units by the fluidics assembly.

3. The system of claim 2, wherein the gasket is configured to be engaged with the microfluidic device such that an orifice of the gasket overlaps each droplet well.

4. The system of claim 1, wherein the instrument is configured to receive an actuation signal from a user, and wherein the actuation signal causes the instrument, without any further user input or participation, to apply the pressure, to monitor the pressure, and to stop application of the pressure.

5. The system of claim 1, wherein the fluidics assembly includes a pump that functions as a source of the pressure, and wherein the pressure is applied by the instrument to the emulsion formation units while the pump is fluidically isolated from the emulsion formation units.

6. The system of claim 1, wherein the instrument is configured to apply negative pressure to the droplet wells of the emulsion formation units.

7. The system of claim 1, wherein each emulsion formation unit includes an oil well to hold a continuous phase for an emulsion, and wherein the instrument is configured to apply positive pressure to the sample wells and the oil wells of the emulsion formation units.

8. The system of claim 1, wherein the instrument is configured to apply pressure to the emulsion formation units with a gas phase that contacts liquid contained by the microfluidic device.

9. The system of claim 8, wherein the gas phase is composed of air.

10. The system of claim 1, wherein the fluidics assembly includes a manifold providing a plurality of ports through which a negative pressure is applied to the droplet wells.

11. The system of claim 1, wherein the instrument is configured to concentrate the emulsions by selectively driving a continuous phase of an emulsion from each of the droplet wells.

12. The system of claim 1, wherein the fluidics assembly includes a valve, and wherein adjustment of the valve stops application of the pressure to all of the emulsion formation units.

13. The system of claim 12, wherein the fluidics assembly includes a pump operatively connected to a reservoir, wherein the reservoir is configured to apply a negative pressure to the droplet wells while fluidically isolated from the pump, and wherein adjustment of the valve fluidically isolates the reservoir from the emulsion formation units.

14. The system of claim 12, wherein the adjustment of the valve vents the droplet wells.

15. A method of emulsion formation performed with the system of claim 1, the method comprising:

applying pressure with the fluidics assembly to the emulsion formation units, to drive droplet formation at the channel intersections and collection of emulsions of the droplets in the droplet wells;

monitoring the pressure with the pressure sensor; and

stopping application of the pressure when the change in pressure is detected.